Cigarette smoking is recognized as the most important factor in the development of chronic airflow obstruction, yet only a minority of cigarette smokers develop clinical disease. Recently, interest has been focused on the role of increased levels of airways responsiveness and atopy as possible potentiating factors for the development of chronic airflow obstruction. Current epidemiologic studies have data on only one of these potential risk factors or are too small to adequately address the issues involved. The present study will assess both airways responsiveness (measured by response to methacholine inhalation) and atopy (measured by skin test, blood eosinophilia, and Serum IgE) in an existing cohort of adult males. The study uses the population and data base of the VA Normative Aging Study (NAS) which was begun in 1963. The population consists of over 1900 men originally selected for good health. The NAS currently administers a cigarette smoking history, the NBLBI-ATS respiratory symptoms questionnaire, and spirometry at regularly scheduled examinations, 3 years apart. We will assess airways responsiveness and atopy in 800 participants when they return for their next two examinations. These data will be used to examine the relationship of airways responsiveness, atopy and cigarette smoking to respiratory symptoms and pulmonary function both cross-sectionally and longitudinally. The proposed study would be the only investigation to have data on both airways responsiveness and atopy on a sizeable cohort of subjects. A prospective evaluation of these two potential risk factors, along with cigarette smoking, would establish the relative importance of these variables in the production of chronic airflow obstruction.